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Irreversible conversion of xanthine dehydrogenase into xanthine oxidase by a mitochondrial protease

Irreversible conversion of xanthine dehydrogenase (XDH) to its oxygen free radical producing oxidase (XO) form occurs through an uncharacterized proteolytic process, which was studied in human liver. Upon incubation of fresh unfrozen liver cytosol, XDH remained intact. When recombinant human XDH was...

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Bibliographic Details
Published in:FEBS letters 1999-01, Vol.443 (2), p.117-120
Main Authors: Saksela, Mika, Lapatto, Risto, Raivio, Kari O
Format: Article
Language:English
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Summary:Irreversible conversion of xanthine dehydrogenase (XDH) to its oxygen free radical producing oxidase (XO) form occurs through an uncharacterized proteolytic process, which was studied in human liver. Upon incubation of fresh unfrozen liver cytosol, XDH remained intact. When recombinant human XDH was coincubated with subcellular fractions of human liver, the mitochondrial intermembrane space was shown to contain a heat-labile activity that converted XDH irreversibly to XO. This activity is resistant to inhibitors of all major groups of proteases. We postulate that this novel type of proteolytic enzyme is released into the cytosol upon mitochondrial damage.
ISSN:0014-5793
1873-3468
DOI:10.1016/S0014-5793(98)01686-X